A new fusion peptide, AQB-565, may hold promise as a novel treatment for infantile spasms that is similarly as effective as adrenocorticotropic hormone (ACTH) but with potentially fewer side effects, according to study results published in Epilepsy Research.
Although epileptic spasms during infancy (also called infantile spasms or West syndrome) are extremely rare, they represent a serious treatment and social problem. While these spasms can rarely be controlled with classic anti-seizure medications, current treatments include hormonal therapy or vigabatrin (by itself or in combination).
Because these treatments are only partially effective and have significant side effects, new treatments for this condition are needed. A novel melanocortin fusion peptide developed by Aequus Biopharma, AQB-565, has been optimized for treatment of inflammatory diseases.
It includes the first 24 amino acids of ACTH; however, in contrast to ACTH, AQB-565 is preferentially active on the central melanocortin receptors, MC3 and MC4. It also contains an amino acid linker and the NDP-MSH molecule (a melanocyte-stimulating hormone analogue with asparagine, aspartate, and proline as the initial 3 of the 13 amino acids).
Researchers compared the efficacy of AQB-565 with equivalent doses of ACTH in a rat model of infantile spasms consisting of prenatal exposure to betamethasone and repeated postnatal trigger spasms with N-methyl-D-aspartic acid (NMDA).
They found that all doses of ACTH, and all doses but one of AQB-565 in the same range, suppressed spasms throughout the study. They also found that there was no dose-dependent effect and that both compounds had an “all-or-none” effect that is similar to the clinical outcome of hormonal treatment of infantile spasms in children.
“Our current study shows that the new fusion peptide, AQB-565, consisting of a combination of ACTH(1-24) and NDP-MSH effectively suppresses spasms in the rat model of epileptic spasms in infancy,” concluded the investigators.
Chern C-R, Chern C-J, Velíšková J, Velíšek L. AQB-565 shows promise in preclinical testing in the model of epileptic spasms during infancy: Head-to-head comparison with ACTH. Epilepsy Res. 2019;152:31-34.